The Z-Profile Study: a multicenter, retrospective cohort study to assess the real-world use and effectiveness of elbasvir/grazoprevir in Canadian adult patients with chronic hepatitis C.

Background: Canada was the first country to approve elbasvir/grazoprevir (EBR/GZR) for the treatment of chronic HCV infection for genotypes 1 and 4 with or without ribavirin and genotype 3 with sofosbuvir, with no recommendation for baseline resistance testing. The aim of this study was to describe the effectiveness of EBR/GZR and the profile of patients selected for treatment in a Canadian real-world setting.
Methods: This multicenter retrospective study of HCV-infected patients treated with EBR/GZR took place among selected Canadian health care providers, with no exclusion criteria. Primary outcome measures included parameters associated with patient profile and sustained virologic response at 12 weeks (SVR12) and 24 weeks after treatment.
Results: A total of 408 patients were included; 244 had available SVR12 information (per-protocol population [PP]). Genotype distribution included 1a (54.7%), 1b (17.2%), 3 (11.8%), 4 (10.0%), and other (6.4%). The majority (88.7%) of participants were treated for 12 weeks without ribavirin. Fifty-nine (14.5%) participants, predominantly with genotype 1a (49/59) infection, were tested for baseline resistance-associated substitutions (bRAS). SVR12 was achieved by 95.9% of the PP. In an exploratory analysis assessing potential predictors of SVR12, participants who had undergone bRAS testing (OR 0.14, 95% CI 0.03-0.64) and participants who had undergone liver transplant (OR 0.05, 95% CI 0.00-0.68) had significantly lower odds of achieving SVR12.
Conclusions: This study supports the real-world effectiveness of EBR/GZR-including a broad range of genotypes and diverse fibrosis stages-in the absence of bRAS testing and in special populations.
Competing Interests: ET reports grants/personal fees from Merck Canada, AbbVie, and Gilead and personal fees from BMS and Pendopharm. JT reports no conflict of interest. CF reports grants from ViiV Healthcare and AbbVie. BC reports grants/honoraria from AbbVie, Gilead, and Merck. AR reports grants/personal fees/other from AbbVie and Merck and other from Allergen, Arbutus, and Assembly Bio; research/grants/personal fees and other from Gilead Sciences; personal fees/other from Janssen; and other from Novartis. SB reports other from Merck Canada; personal fees from Merck Canada; and grants from Gilead Canada. KT reports grants from Merck Canada and personal fees from AbbVie, Gilead Sciences, and Merck. EMY reports grants from Merck Canada, Gilead Sciences, AbbVie, Merck Inc., Janssen, Intercept, Genfit, and Springbank and personal fees from AbbVie, Gilead Canada, Merck Canada, and Celgene Canada. BR reports grants from Merck Canada and personal fees from AbbVie, Shire, Merck Canada, Takeda, Allergan, and Ferring. GM reports grants from Merck Canada and support from the HCV program at CUPS from Merck, Gilead, AbbVie, and Coverdale. AW reports grants/personal fees from Merck Canada, Gilead Sciences Canada, and AbbVie. CC reports grants/personal fees and non-financial support from Merck and grants/personal fees/non-financial support from Gilead and AbbVie. KP reports personal fees from Merck and Gilead Sciences. MP reports personal fees from Merck, Gilead, and AbbVie. KS reports grants/personal fees from Merck, Gilead, and AbbVie. BT reports no conflict of interest. LD reports grants from Gilead and Merck and personal fees from AbbVie, Gilead, and Merck. KD reports grants from Merck and Gilead and other from AbbVie. PG reports personal fees from Merck. SSL reports grants/personal fees from AbbVie, Intercept, Gilead, and Merck and grants from BMS. JHB and JBT were employed by Merck Canada Inc at time of study.
(Copyright © 2020 Canadian Association for the Study of the Liver.)